Shilatifard, A. Chromatin Modifications by Methylation and Ubiquitination: Implications in the Regulation of Gene Expression. Annu. Rev. Biochem. 75, 243-269

Saint Louis University School of Medicine and the Saint Louis University Cancer Center, St. Louis, Missouri 63104, USA.
Annual Review of Biochemistry (Impact Factor: 30.28). 02/2006; 75(1):243-69. DOI: 10.1146/annurev.biochem.75.103004.142422
Source: PubMed


It is more evident now than ever that nucleosomes can transmit epigenetic information from one cell generation to the next. It has been demonstrated during the past decade that the posttranslational modifications of histone proteins within the chromosome impact chromatin structure, gene transcription, and epigenetic information. Multiple modifications decorate each histone tail within the nucleosome, including some amino acids that can be modified in several different ways. Covalent modifications of histone tails known thus far include acetylation, phosphorylation, sumoylation, ubiquitination, and methylation. A large body of experimental evidence compiled during the past several years has demonstrated the impact of histone acetylation on transcriptional control. Although histone modification by methylation and ubiquitination was discovered long ago, it was only recently that functional roles for these modifications in transcriptional regulation began to surface. Highlighted in this review are the recent biochemical, molecular, cellular, and physiological functions of histone methylation and ubiquitination involved in the regulation of gene expression as determined by a combination of enzymological, structural, and genetic methodologies.

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    • "Notably, both SAM and SAH are depleted under these conditions. To test whether these alterations were sufficient to induce changes in histone methylation, we considered the relative levels of several histone methylation marks involving trimethylation at lysines 4,9, 27 that are each known to have substantial roles defining chromatin states, most notably at active and inactive genes, and mediating gene expression (Shilatifard, 2006) (Figure 1C). In addition, the kinetic properties, such as SAM binding affinity (K m ), of these histone methyltransferases (An et al., 2011; Chin et al., 2005; Horiuchi et al., 2013; Obianyo et al., 2008; Patnaik et al., 2004; Xiao et al., 2003) suggests SAM concentration may play a role in their regulation and directly affect the rate of histone methylation reactions in the cell (Figure S1A). "
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    • "The association between MED23 and RNF20/40 establishes a mechanistic link between the Mediator complex and epigenetic regulation during transcription, which may provide further insight into the roles that the Mediator complex plays in (i) crosstalk between multiple histone modifications, (ii) transcription elongation , (iii) histone modifications and cancer, and (iv) mRNA processing , as we discuss here. Firstly, previous studies regarding trans-histone modification crosstalk indicate that a strict linkage exists between ubiquitinated H2B and histone H3 methylation (Dover et al, 2002; Shilatifard, 2006; Kim et al, 2013; Wu et al, 2013). However, other studies suggest that H2Bub is independent of H3 methylation (Tanny et al, 2007; Lee et al, 2012). "
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    • "Here, we report PAF1 as being an evolutionarily conserved factor that contributes significantly to the process of pause release by Pol II. PAF1 was originally identified biochemically as a factor co-purifying with Pol II from yeast extracts (Shi et al., 1996; Wade and Jaehning, 1996), and the role of PAF1 and its complex, in serving as a platform for co-transcriptional histone-modifying enzymes and RNA-processing factors, is highly conserved from yeast to humans (Krogan et al., 2003; Shilatifard 2006). Our studies in mammalian cells reveal that the loss of PAF1 leads to widespread release of the promoter-proximal paused Pol II into gene bodies. "
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